Ribonucleic acid ligands, or aptamers, are a class of drug compounds ideally suited to anticoagulation therapy. They bind to their targets with high affinity and specificity, are only slightly immunogenic and their bioavailability can be tailored to suit a particular clinical need (Nimjee et al, Annu. Rev. Med. 56:555-583(2005)). More recently, research has shown that these drugs can be controlled with antidotes both in vitro and in vivo (Nimjee et al, Molecular Therapy: the Journal of the American Society of Gene Therapy (2006), Mol. Ther. 14:408-45 Epub Jun. 9, 2006, Rusconi et al, Nat. Biotechnol. 22:1423-1428 (2004), Rusconi et al, Nature 419:90-94 (2002)).
Millions of Americans received antiplatelet agents to prevent pathological clot formation (thrombosis). However, these compounds carry a risk of increased bleeding and have no antidote to rapidly reverse activity. Recent studies with antibodies have indicated that blocking GPVI function may protect individuals from thrombosis without an increased risk of bleeding.
The present invention results, at least in part, from studies designed to identify aptamers that bind to GPVI and modulate (inhibit or enhance) its function and/or activity. Aptamers that inhibit GPVI function/activity can be used, for example, therapeutically to inhibit platelet aggregation. Aptamers that enhance GPVI function/activity can be used, for example, to activate platelets; such aptamers can be used in studies designed elucidate the mechanism of GPVI receptor activation.